H2O2-induced apoptosis

Antunes F, Cadenas E (2001) Cellular titration of apoptosis with steady state concentrations of H2O2 submicromolar levels of H2O2 induce apoptosis through Fenton chemistry independent of the cellular thiol state. Free Radic Biol Med 30 1008-1018... 

The flavonol quercetin has been the subject of much interest in terms of its beneficial properties against oxidative stress [62] and has been shown to exert a potent protective actions against hydrogen peroxide-induced apoptosis of rat thymocytes [63] and cell death in rat hepatocytes (BL-9) [60], as well as reducing oxidative stress and cell damage in fiver tumor cells induced by AAPH (2,2-azobis(2-aminopropane) dihydrochloride) [64]. Quercetin and another flavonol, kaempferol, as well as catechin and the flavone taxifolin, have been observed to suppress the cytotoxicity of 02 and H2O2 to Chinese hamster V79 cells, as assessed by the ability of the flavonoids to prevent the decrease in the number of cell colonies induced by the oxidants [65]. Furthermore, quercetin has been shown to protect cutaneous tissue-associated cells (human skin fibroblasts, keratinocytes, and endothelial cells) from oxidative injury induced by buthionine sulfoximine (BSO), an inhibitor of GSH synthesis [66]. 

Park et al. (2002) demonstrated that cytosolic elevation is an earlier signaling event in apoptosis of HCT-15 cells. DADS can induce apoptosis in HCT-15 cells through the sequential mechanism of Ca homeostasis disruption, accumulation of H2O2, and resulting caspase-3 activation. 

Polyamine analogs for cancer therapy often induce apoptosis, but so far the mechanisms have not been satisfactorily defined. Elevated levels of H2O2 as a byproduct of the catabolism of polyamines by spermine/spermidine acetyl-transferase (SSAT) are assumed to induce apoptosis by oxidative stress. In a recent study, Chen et al. demonstrated that a suppression of SSAT prevented the depletion of polyamine pools by polyamine analog-induced apoptosis in human melanoma cells [101]. The observation that this phenomenon is mainly related to the polyamine analogs opens a new route for the development of novel analogs inhibiting the SSAT induction that could lead to the disruption of the tumor, but not generally of normal tissues. 

The effect of antioxidant sodium ferulate on human lymphocytes FA082 apoptosis induced by H2O2. Zhongguo Yi Xue Ke Xue Yuan Xue Bao 1998 ... 

Tamagno E., Robino G., Obbili A., Bardini R, Aragno M., Parola M., and Danni O. (2003). H2O2 and 4-hydroxynonenal mediate amyloid beta-induced neuronal apoptosis by activating JNKs and pSS K. Exp. Neurol. 180 144-155. 

Watson AJ, Askew JN, Benson RS. Polyfadenosine diphosphate ribose) polymerase inhibition prevents necrosis induced by H2O2 but not apoptosis. Gastroenterology 1995 109 472-82. 

As a consequence of these conditions, the levels of ROS such as superoxide anion radical (02 ), hydrogen peroxide (H2O2), and hydroxyl radical ("OH) are increased (Lushchak, 2014). They inactivate the mitochondrial enzymes, directly damage DNA, DNA repair enzymes, lipid peroxidation, cyt c release, and transcription factors leading to apoptosis/ceU death. Figure 3.9 illustrates the ROS/RNS-induced oxidative damage in proteins, lipids, and DNA. 

However, the mechanism by which apoptosis is induced has not been defined. As described in Sect. 2.3.4, the catalysis of polyamines produces H2O2 as a byproduct, suggesting that apoptosis may be, in part, due to oxidative stress [134]. Treatment with other polyamine analogs revealed that multiple apoptotic mechanisms were involved. Typical features of apoptosis including cytochrome c release, activation of caspase-3, and cleavage of poly(ADP-ribose) polymerase (PARP) occur after treatment of tumor cells. 

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